Disease progression of human SOD1 (G93A) transgenic ALS model rats

Authors

  • Arifumi Matsumoto,

    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
    2. Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
    3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan
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  • Yohei Okada,

    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
    2. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
    3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan
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  • Masanori Nakamichi,

    1. Takeda Chemical Industries, Ltd., Osaka, Japan
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  • Masaya Nakamura,

    1. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
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  • Yoshiaki Toyama,

    1. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
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  • Gen Sobue,

    1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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  • Makiko Nagai,

    1. Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Masashi Aoki,

    1. Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Yasuto Itoyama,

    1. Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Hideyuki Okano

    Corresponding author
    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
    2. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan
    • Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Abstract

The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies. © 2005 Wiley-Liss, Inc.

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